Browsing by Author "Cheung, Winson Y."

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    Integrating Systemic Therapies into the Multimodality Treatment of Resectable Colorectal Liver Metastases
    (2018-06-21) Abdel-Rahman, Omar; Cheung, Winson Y.
    Colorectal carcinoma (CRC) is one of the most common cancers worldwide. A considerable proportion of CRC patients may present with metastatic disease either at upfront presentation (synchronous with the primary) or following diagnosis and treatment of the primary tumor (metachronous). Management of CRC liver metastases is a challenging endeavor which frequently necessitates proper assessment of patient- and disease-related factors. There is an opportunity within the management of CRC liver metastases to incorporate multiple treatment modalities (including surgery, other locoregional treatments, and systemic therapy). The current review aims to provide an updated overview on the optimal management strategy for CRC patients with liver metastases with a specific focus on the integration of systemic and/or locoregional treatments among patients with resectable or potentially resectable disease.
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    Long-Term Opioid Prescribing among Patients Living with Metastatic Cancer as a Chronic Disease
    (2024-10-28) Harsanyi, Hannah; Cuthbert, Colleen; Yang, Lin; Lau, Jenny; Cheung, Winson Y.
    Patients living with metastatic cancer often experience pain which requires involvement of palliative care and symptom management teams. Opioids are a commonly used tool for the treatment of this cancer-related pain. While opioids serve an important purpose in symptom management and end-of-life care, harms related to their use are increasingly recognized as having a significant impact on patients with cancer. This changing perception has resulted from a growing body of literature investigating opioid-related harms, such as long-term prescribing, opioid-related healthcare utilization, and nonmedical use within cancer populations. However, many of these studies exclude patients with metastatic disease, and very few specifically investigate this population. The work reported in this thesis aims to address this knowledge gap by reviewing perceptions of opioid use among patients with metastatic disease, investigating the incidence of opioid-related hospitalizations and emergency department visits among recipients of long-term opioid prescribing, and determining the contribution of nonmedical opioid use to these encounters. Based on a review of previously published literature, stigmatization of opioid use was identified as a significant barrier to effective cancer pain management. Patients reported fears of addiction, tolerance, and side-effects which led to opioid-restricting behaviours. Despite these reported concerns, a large proportion of patients in Alberta received long-term opioid prescribing, with 23% of opioid-naïve patients with chronic metastatic disease being affected. Among these patients, the incidence of opioid-related healthcare encounters was higher than that reported in other cancer populations and was significantly associated with higher dosage and concurrent prescribing of psychoactive medications. Increased implementation of harm-reduction measures may be useful to mitigate this risk. From reviewing medical records of patients who experienced opioid-related healthcare encounters, nonmedical opioid use was identified as a possible contributing factor for 35% of patients. However, a majority of encounters were not primarily attributable to nonmedical opioid use and many patients experienced poorly controlled pain and displayed possible manifestations of opioid stigma. While risk assessment for nonmedical opioid use is important for patients receiving long-term opioid prescribing, it should be conducted in a non-stigmatizing manner which encourages patients to prioritize effective management of their pain.
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    New method for determining breast cancer recurrence-free survival using routinely collected real-world health data
    (2022-03-16) Jung, Hyunmin; Lu, Mingshan; Quan, May L.; Cheung, Winson Y.; Kong, Shiying; Lupichuk, Sasha; Feng, Yuanchao; Xu, Yuan
    Abstract Background In cancer survival analyses using population-based data, researchers face the challenge of ascertaining the timing of recurrence. We previously developed algorithms to identify recurrence of breast cancer. This is a follow-up study to detect the timing of recurrence. Methods Health events that signified recurrence and timing were obtained from routinely collected administrative data. The timing of recurrence was estimated by finding the timing of key indicator events using three different algorithms, respectively. For validation, we compared algorithm-estimated timing of recurrence with that obtained from chart-reviewed data. We further compared the results of cox regressions models (modeling recurrence-free survival) based on the algorithms versus chart review. Results In total, 598 breast cancer patients were included. 121 (20.2%) had recurrence after a median follow-up of 4 years. Based on the high accuracy algorithm for identifying the presence of recurrence (with 94.2% sensitivity and 79.2% positive predictive value), the majority (64.5%) of the algorithm-estimated recurrence dates fell within 3 months of the corresponding chart review determined recurrence dates. The algorithm estimated and chart-reviewed data generated Kaplan–Meier (K-M) curves and Cox regression results for recurrence-free survival (hazard ratios and P-values) were very similar. Conclusion The proposed algorithms for identifying the timing of breast cancer recurrence achieved similar results to the chart review data and were potentially useful in survival analysis.
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    Predicting Early Discontinuation of Adjuvant Chemotherapy and its Impact on Survival among Individuals with Stage III Colon Cancer
    (2020-08-05) Boyne, Devon J; Brenner, Darren R.; Friedenreich, Christine M.; Cheung, Winson Y.; Hilsden, Robert J.; Sajobi, Tolulope T.
    Background: Approximately one in three patients with stage III colon cancer fail to complete the entirety of their adjuvant chemotherapy prescription. Two questions arise from this observation: 1) Can we predict which patients will discontinue adjuvant chemotherapy? and 2) Does a shortened duration of adjuvant chemotherapy impact overall survival? Evidence pertaining to the first question is limited. While question two was recently addressed within a large randomized trial, results from this trial have been controversial. Methods: To address question one, we conducted a systematic review and survey of medical oncologists to identify factors that predict non-completion of adjuvant chemotherapy. Building upon the results of this investigation, we developed an online calculator to predict the risk of discontinuation at the individual-level. For question two, a systematic review and meta-analysis was performed. In addition, we emulated a target trial that examined the effect of a shortened duration of adjuvant chemotherapy on overall survival using real-world data.Results: According to a systematic review of 18 studies and survey of 14 medical oncologists, there was evidence that increased comorbidity, worse performance status, higher T stage, and adjuvant CAPOX chemotherapy or poor oxaliplatin candidacy were associated with an increased risk of discontinuation. Using information from 1,378 patients, an online risk calculator was developed. Internal validation suggested that this calculator accurately predicted and classified patients with respect to their risk of discontinuation (optimism-adjusted C-statistic=0.80; 95% CI:0.79-0.82; calibration plots were within acceptable limits). A meta-analysis of 22 studies suggested that a shortened duration of adjuvant chemotherapy was harmful among patients prescribed a monotherapy (HR: 0.59; 95% CI: 0.52-0.68) but not among among those prescribed FOLFOX or CAPOX (HR: 0.80; 95% CI: 0.58-1.09). In a target trial analysis of 485 colon cancer patients, both the overall and subgroup-specific hazard ratios were consistent with those from a randomized trial. Conclusions: Results from this investigation can help assess and communicate the risk of early discontinuation within this study population. Results from our meta-analysis and target trial emulation suggest that a shortened duration of adjuvant chemotherapy may be appropriate for some patients which supports findings from a recent randomized trial.
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    Text analysis framework for identifying mutations among non-small cell lung cancer patients from laboratory data
    (2024-03-11) Yusuf, Amman; Boyne, Devon J.; O’Sullivan, Dylan E.; Brenner, Darren R.; Cheung, Winson Y.; Mirza, Imran; Jarada, Tamer N.
    Abstract Background Laboratory data can provide great value to support research aimed at reducing the incidence, prolonging survival and enhancing outcomes of cancer. Data is characterized by the information it carries and the format it holds. Data captured in Alberta’s biomarker laboratory repository is free text, cluttered and rouge. Such data format limits its utility and prohibits broader adoption and research development. Text analysis for information extraction of unstructured data can change this and lead to more complete analyses. Previous work on extracting relevant information from free text, unstructured data employed Natural Language Processing (NLP), Machine Learning (ML), rule-based Information Extraction (IE) methods, or a hybrid combination between them. Methods In our study, text analysis was performed on Alberta Precision Laboratories data which consisted of 95,854 entries from the Southern Alberta Dataset (SAD) and 6944 entries from the Northern Alberta Dataset (NAD). The data covers all of Alberta and is completely population-based. Our proposed framework is built around rule-based IE methods. It incorporates topics such as Syntax and Lexical analyses to achieve deterministic extraction of data from biomarker laboratory data (i.e., Epidermal Growth Factor Receptor (EGFR) test results). Lexical analysis compromises of data cleaning and pre-processing, Rich Text Format text conversion into readable plain text format, and normalization and tokenization of text. The framework then passes the text into the Syntax analysis stage which includes the rule-based method of extracting relevant data. Rule-based patterns of the test result are identified, and a Context Free Grammar then generates the rules of information extraction. Finally, the results are linked with the Alberta Cancer Registry to support real-world cancer research studies. Results Of the original 5512 entries in the SAD dataset and 5017 entries in the NAD dataset which were filtered for EGFR, the framework yielded 5129 and 3388 extracted EGFR test results from the SAD and NAD datasets, respectively. An accuracy of 97.5% was achieved on a random sample of 362 tests. Conclusions We presented a text analysis framework to extract specific information from unstructured clinical data. Our proposed framework has shown that it can successfully extract relevant information from EGFR test results.
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    The influence of adjuvant chemotherapy dose intensity on overall survival in resected colon cancer: a multicentered retrospective analysis
    (2022-11-01) Breadner, Daniel; Loree, Jonathan M.; Cheung, Winson Y.; Gipson, Meghan; Lakkunarajah, Suganija; Mulder, Karen E.; Spartlin, Jennifer L.; Kong, Shiying; Ding, Philip Q.; Gill, Sharlene; Welch, Stephen A.
    Abstract Background Colorectal cancer remains the second leading cause of cancer death in North America. Fluorouracil and oxaliplatin based adjuvant chemotherapy for resected colon cancer (CC) reduces cancer recurrence, but also causes significant toxicity requiring dose reductions. The effect of dose intensity on survival outcomes is not fully understood and strengthening the evidence supports informed decision making between patients and oncologists. Methods Patients treated with adjuvant chemotherapy, between 2006 and 2011, for resected colon cancer at four Canadian academic cancer centers were retrospectively analyzed. All patients must have received oxaliplatin with either capecitabine (CAPOX) or 5-FU (FOLFOX). Dose intensity (DI) was calculated as total delivered dose of an individual chemotherapy agent divided by the cumulative intended dose of that agent. The influence of DI on overall survival was examined. Results Five hundred thirty-one patients with high-risk stage II or stage III resected CC were eligible and included in the analysis. FOLFOX was the most common regimen (69.6%) with 29.7% of patients receiving CAPOX and 0.7% receiving both therapies. Median follow-up was 36.7 months. The median DI for 5-FU and capecitabine was 100% and 100% with 13.6% and 9.8% of patients receiving ≤ 80% DI, respectively. The median DI of oxaliplatin was 70% with 56.8% of patients receiving ≤ 80% DI. A DI of > 80% for each chemotherapy component was associated with a significant improvement in overall survival compared to those with a DI of ≤ 80% (5-FU HR = 0.23, 95% CI = 0.08–0.65, p = 0.006; capecitabine HR = 0.56, 95% CI = 0.33–0.94, p = 0.026; oxaliplatin HR = 0.52, 95% CI = 0.33–0.82, p = 0.005). Patients with T2 and/or N2 disease with an oxaliplatin DI > 80% had a trend towards improved survival (HR = 0.62, 95% CI = 0.38–1.02, p = 0.06). Conclusions In resected CC an adjuvant chemotherapy DI of > 80%, of each chemotherapy agent, is associated with improved overall survival.
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    Trends in treatment patterns and survival outcomes in advanced non-small cell lung cancer: a Canadian population-based real-world analysis
    (2022-03-10) Carroll, Robert; Bortolini, Margherita; Calleja, Alan; Munro, Robin; Kong, Shiying; Daumont, Melinda J.; Penrod, John R.; Lakhdari, Khalid; Lacoin, Laure; Cheung, Winson Y.
    Abstract Background As part of the multi-country I-O Optimise research initiative, this population-based study evaluated real-world treatment patterns and overall survival (OS) in patients treated for advanced non-small cell lung cancer (NSCLC) before and after public reimbursement of immuno-oncology (I-O) therapies in Alberta province, Canada. Methods This study used data from the Oncology Outcomes (O2) database, which holds information for ~ 4.5 million residents of Alberta. Eligible patients were adults newly diagnosed with NSCLC between January 2010 and December 2017 and receiving first-line therapy for advanced NSCLC (stage IIIB or IV) either in January 2010-March 2016 (pre–I-O period) or April 2016-June 2019 (post–I-O period). Time periods were based on the first public reimbursement of I-O therapy in Alberta (April 2017), with a built-in 1-year lag time before this date to allow progression to second-line therapy, for which the I-O therapy was indicated. Kaplan–Meier methods were used to estimate OS. Results Of 2244 analyzed patients, 1501 (66.9%) and 743 (33.1%) received first-line treatment in the pre–I-O and post–I-O periods, respectively. Between the pre–I-O and post–I-O periods, proportions of patients receiving chemotherapy decreased, with parallel increases in proportions receiving I-O therapies in both the first-line (from < 0.5% to 17%) and second-line (from 8% to 47%) settings. Increased use of I-O therapies in the post–I-O period was observed in subgroups with non-squamous (first line, 15%; second line, 39%) and squamous (first line, 25%; second line, 65%) histology. First-line use of tyrosine kinase inhibitors also increased among patients with non-squamous histology (from 26% to 30%). In parallel with these evolving treatment patterns, median OS increased from 10.2 to 12.1 months for all patients (P < 0.001), from 11.8 to 13.7 months for patients with non-squamous histology (P = 0.022) and from 7.8 to 9.4 months for patients with squamous histology (P = 0.215). Conclusions Following public reimbursement, there was a rapid and profound adoption of I-O therapies for advanced NSCLC in Alberta, Canada. In addition, OS outcomes were significantly improved for patients treated in the post–I-O versus pre–I-O periods. These data lend support to the emerging body of evidence for the potential real-world benefits of I-O therapies for treatment of patients with advanced NSCLC.